Dr. Frosch serves as Co-Lead for the ACTC Neuropathology Unit.  He is the Lawrence J. Henderson Associate Professor of Pathology and
Health Sciences & Technology at Harvard Medical School, and Director of the C.S. Kubik Laboratory for Neuropathology at Massachusetts General Hospital, for the MassGeneral Institute for Neurodegenerative Diseases (MIND)

Dr. Frosch’s lab aims to understand cerebral amyloid angiopathy (CAA), using mouse models and human tissue. In this disease, the peptide Ab deposits in the walls of blood vessels and is associated with risk of hemorrhage (“lobar hemorrhages”). This peptide is the same material that forms the plaques of Alzheimer disease, and nearly all patients with Alzheimer disease have pathologic evidence of CAA as well. CAA also occurs in the absence of histologic  evidence of Alzheimer disease, and can present with hemorrhages or with cognitive changes.  In clinicopathologic studies, his lab has found that this latter presentation is associated with the presence of an inflammatory response, often containing giant cells. This subset of patients can have dramatic recoveries of cognitive function after immunosuppressive therapy.

Dr. Frosch and his team are interested in the sequence of events by which Ab is deposited in blood vessels, what factors determine the distribution of involvement, what the consequences are for the cells of the vessel and how this material can respond to therapeutic interventions focused on Ab currently in clinical trials. For in vivo studies, Frosch’s team uses serial multiphoton imaging with specific probes for these various processes and link the spatial and temporal distribution of the pathologic changes with the development of CAA. They complement these studies with work on human autopsy tissue, collected through the Massachusetts Alzheimer Disease Research Center Neuropathology Core. Those samples are examined through combinations of high field ex vivo MRI, optical clearing and volumetric imaging. They are particularly interested in the changes which result in bleeding in the setting of CAA (hemorrhagic strokes) as well as microinfarcts which can markedly impair cognition.

Dr. Frosch also works with a range of collaborators to understand the relationship between neuropathologic findings in the setting of disease — including Alzheimer disease, Parkinson disease, Amyotrophic Lateral Sclerosis and others — and other biochemical or functional markers of disease. These studies include advancing imaging methods (DTI, OCT and others) as well as various genetic studies (deep sequencing as well as GWAS), cell biology and structural biology.

Adam L. Boxer, MD, PhD is the Endowed Professor in Memory and Aging in the Department of Neurology at the University of California, San Francisco (UCSF).  He co-chairs the ACTC Non-Alzheimer’s Dementia Committee.  At UCSF, he directs the Neurosciences Clinical Research Unit and the Alzheimer’s Disease and Frontotemporal Degeneration (FTD) Clinical Trials Program at the UCSF Memory and Aging Center.  Dr. Boxer’s research is focused on developing new treatments and biomarkers for neurodegenerative diseases, particularly those involving tau and TDP-43.  He is the Principal Investigator of the Advancing Research and Treatment for FTLD (ARTFL) Rare Disease Clinical Research Consortium, a collaborative project funded by the National Institutes of Health to create an 18 center North American research network to support the development of new therapies for FTLD. He also leads the Four Repeat Tauopathy Neuroimaging Initiative (4RTNI), a multicenter, longitudinal tau PET and biomarker study focused on PSP and CBD.  He has been the PI for a variety of multicenter, randomized, placebo controlled clinical trials in FTLD spectrum disorders, including memantine for FTLD, davunetide for PSP, TPI-287 for primary and secondary tauopathies, and salsalate for PSP.  He co-chairs the FTLD Treatment Study Group (FTSG) and the PSP Research Roundtable, academic-industry collaborative groups working to speed the development of new therapies for FTLD, CBD and PSP.

Jason Karlawish is a Professor of Medicine, Medical Ethics and Health Policy, and Neurology at Penn and cares for patients at the Penn Memory Center (www.pennmemorycenter.org), which he co-directs. He leads the ACTC Ethics Committee, is a member of the Recruitment and Retention Core and the Steering Committee. At Penn, he leads the Outreach and Recruitment Core and Research Education Component of the ADRC. His research focuses on issues at the intersections of bioethics, aging and the neurosciences. He leads the Penn Program for Precision Medicine for the Brain (P3MB). P3MB developed standards for Alzheimer’s disease biomarker disclosure and investigates the clinical impacts of this knowledge on persons and their families. He has investigated the development and translation of Alzheimer’s disease treatments and biomarker-based diagnostics, informed consent, quality of life, research and treatment decision making, and voting by persons with cognitive impairment and residents of long term care facilities.  P3MB developed the amyloid imaging disclosure process and the SOKRATES Study, originally used in the A4 Study, these have become a template for assuring the safe disclosure of Alzheimer’s disease genes and biomarkers and assessing their impact on persons and their families.

Joshua D. Grill, PhD, is an Associate Professor in the Departments of Psychiatry & Human Behavior and Neurobiology & Behavior at the University of California, Irvine (UCI). He is the Director of the Institute for Memory Impairments and Neurological Disorders (UCI MIND) and the Associate Director of the UCI Alzheimer’s Disease Research Center. He also directs its Outreach, Recruitment, and Engagement Core for the UCI ADRC and is the leader of the Accrual and Retention Consult Service for the UCI Institute for Clinical and Translational Science (ICTS). Dr. Grill serves in several roles for ACTC. He is co-leader of the Recruitment Unit as well as the Internal Ethics Committee. He also serves on the Executive and IDEA-CT Committees. Dr. Grill’s independent research is focused on clinical trial design, recruitment and retention, and research ethics across the spectrum of Alzheimer’s disease.

Clifford R. Jack Jr., M.D., is Co-Lead for the ACTC MRI Unit. Dr. Jack is engaged in brain imaging research in cognitive aging and Alzheimer’s disease and related disorders.  Dr. Jack’s research group employs imaging to study the biology of brain aging and cognitive impairment. They also develop image-processing algorithms for quantitatively measuring the information obtained from brain imaging. They employ a variety of brain imaging modalities including anatomic MRI, MR spectroscopy, functional connectivity MR, diffusion MR, perfusion MR, quantitative susceptibility mapping, FDG PET, amyloid PET, and tau PET. Dr. Jack’s group serves as the MR center for many large multi-site observational and interventional studies.

Dorene M. Rentz, PsyD, is a Professor of Neurology at Harvard Medical School and a clinical neuropsychologist with dual appointments in the Departments of Neurology at Brigham and Women’s Hospital and Massachusetts General Hospital. She serves as the co-lead with Dr. Ron Petersen of the ACTC Clinical Outcome Instrument Unit and with Dr. Steve Salloway as co-lead of the ACTC-IDEA-CT Mentoring Sub-committee. She is also the Co-Director of the Center for Alzheimer Research and Treatment and the Director of the Outreach, Recruitment and Engagement Core at the Massachusetts Alzheimer’s Disease Research Center and is the Clinical Core Leader of the Harvard Aging Brain Study. Her research focus has been on the early detection of preclinical Alzheimer’s disease, particularly in high functioning individuals. Her recent work involves exploring early cognitive changes using PET amyloid and tau imaging. More recently, she is a leader in cognitive outcome assessments for secondary prevention trials in Preclinical Alzheimer’s disease and has explored the feasibility of using technology to do cognitive assessments in the clinic and home environments.